van Agtmaal Marnix J M, Houben Alfons J H M, Pouwer Frans, Stehouwer Coen D A, Schram Miranda T
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands2Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Department of Psychology, University of Southern Denmark, Odense, Denmark.
JAMA Psychiatry. 2017 Jul 1;74(7):729-739. doi: 10.1001/jamapsychiatry.2017.0984.
The etiologic factors of late-life depression are still poorly understood. Recent evidence suggests that microvascular dysfunction is associated with depression, which may have implications for prevention and treatment. However, this association has not been systematically reviewed.
To examine the associations of peripheral and cerebral microvascular dysfunction with late-life depression.
A systematic literature search was conducted in MEDLINE and EMBASE for and longitudinal studies published since inception to October 16, 2016, that assessed the associations between microvascular dysfunction and depression.
Three independent researchers performed the study selection based on consensus. Inclusion criteria were a study population 40 years of age or older, a validated method of detecting depression, and validated measures of microvascular function.
This systematic review and meta-analysis has been registered at PROSPERO (CRD42016049158) and is reported in accordance with the PRISMA and MOOSE guidelines. Data extraction was performed by an independent researcher.
The following 5 estimates of microvascular dysfunction were considered in participants with or without depression: plasma markers of endothelial function, albuminuria, measurements of skin and muscle microcirculation, retinal arteriolar and venular diameter, and markers for cerebral small vessel disease. Data are reported as pooled odds ratios (ORs) by use of the generic inverse variance method with the use of random-effects models.
A total of 712 studies were identified; 48 were included in the meta-analysis, of which 8 described longitudinal data. Data from 43 600 participants, 9203 individuals with depression, and 72 441 person-years (mean follow-up, 3.7 years) were available. Higher levels of plasma endothelial biomarkers (soluble intercellular adhesion molecule-1: OR, 1.58; 95% CI, 1.28-1.96), white matter hyperintensities (OR, 1.29; 95% CI, 1.19-1.39), cerebral microbleeds (OR, 1.18; 95% CI, 1.03-1.34), and cerebral (micro)infarctions (OR, 1.30; 95% CI, 1.21-1.39) were associated with depression. Among the studies available, no significant associations of albuminuria and retinal vessel diameters with depression were reported. Longitudinal data showed a significant association of white matter hyperintensities with incident depression (OR, 1.19; 95% CI, 1.09-1.30).
This meta-analysis shows that both the peripheral and cerebral forms of microvascular dysfunction are associated with higher odds of (incident) late-life depression. This finding may have clinical implications because microvascular dysfunction might provide a potential target for the prevention and treatment of depression.
人们对老年期抑郁症的病因仍知之甚少。最近的证据表明，微血管功能障碍与抑郁症有关，这可能对预防和治疗具有重要意义。然而，这种关联尚未得到系统的综述。
探讨外周和脑微血管功能障碍与老年期抑郁症之间的关联。
在MEDLINE和EMBASE数据库中进行了系统的文献检索，纳入自数据库建立至2016年10月16日发表的纵向研究，这些研究评估了微血管功能障碍与抑郁症之间的关联。
由三名独立研究人员根据共识进行研究选择。纳入标准为研究人群年龄在40岁及以上、检测抑郁症的有效方法以及微血管功能的有效测量指标。
本系统综述和荟萃分析已在国际前瞻性系统评价注册库（PROSPERO，注册号：CRD42016049158）注册，并按照系统评价和荟萃分析的首选报告项目（PRISMA）和流行病学观察性研究的Meta分析（MOOSE）指南进行报告。数据提取由一名独立研究人员完成。
在有或无抑郁症的参与者中，考虑了以下5种微血管功能障碍的评估指标：内皮功能的血浆标志物、蛋白尿、皮肤和肌肉微循环测量、视网膜动静脉直径以及脑小血管疾病标志物。数据以合并比值比（OR）的形式报告，采用通用逆方差法和随机效应模型。
共识别出712项研究；48项纳入荟萃分析，其中8项描述了纵向数据。可获得来自43600名参与者的数据，其中9203人患有抑郁症，随访总人年数为72441人年（平均随访3.7年）。血浆内皮生物标志物（可溶性细胞间黏附分子-1：OR = 1.58；95%置信区间[CI]，1.28 - 1.96）、白质高信号（OR = 1.29；95% CI，1.19 - 1.39）、脑微出血（OR = 1.18；95% CI，1.03 - 1.34）和脑（微）梗死（OR = 1.30；95% CI，1.21 - 1.39）水平较高与抑郁症相关。在现有研究中，未报告蛋白尿和视网膜血管直径与抑郁症有显著关联。纵向数据显示白质高信号与新发抑郁症有显著关联（OR = 1.19；95% CI，1.09 - 1.30）。
这项荟萃分析表明，外周和脑微血管功能障碍形式均与（新发）老年期抑郁症的较高发病几率相关。这一发现可能具有临床意义，因为微血管功能障碍可能为抑郁症的预防和治疗提供一个潜在靶点。
